ABCB1和CYP2C19基因多态性与动脉粥样硬化性脑梗死患者氯吡格雷疗效的相关性

目的:探讨在急性动脉粥样硬化性脑梗死患者中,不同ABCB1和CYP2C19基因型对氯吡格雷抗血小板疗效的影响。方法:纳入115例发病7 d内住院的急性动脉粥样硬化性脑梗死患者,根据CYP2C19基因型分为3组:快代谢型、中代谢型、慢代谢型;根据ABCB1基因型分为野生型和突变型。再根据ABCB1和CYP2C19两种基因突变的数量,将入组患者分为A组(两个基因均无突变)、B组(其中一个基因发生突变)和C组(两个基因均发生突变)。所有患者均予以卒中单元常规治疗,利用血栓弹力图仪(thromb elasto gram, TEG)检测患者服用氯吡格雷7 d后的血小板功能及血小板药物抑制率,并在患者入院时及服用氯吡格雷治疗7 d后进行神经功能评估,包括美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale, NIHSS)及改良Rankin量表(modified rankin scale, mRS)。结果:CYP2C19基因快代谢型、中代谢型、慢代谢型分别有46例、48例(其中*1/*2 40例,*1/*3 8例)、21例(其中*2/*2 18例,*2/*3 3例);ABCB1野生型49例,突变型66例;A、B、C组患者分别有23例、50例、42例。不同ABCB1、CYP2C19基因型及含不同基因突变数量患者中,血小板药物抑制率、血小板功能及急性期神经功能变化情况差异均无统计学意义。结论:在本研究所纳入的急性动脉粥样硬化性脑梗死人群中,未发现ABCB1、CYP2C19基因多态性对氯吡格雷疗效的影响。     

CYP1A2*1F基因多态性与肺癌术后化疗疗效及预后的关系

[目的] 探讨细胞色素P4501A2(CYP1A2)*1F基因多态性与肺癌术后化疗疗效及预后的关系.[方法]对100例肺癌患者进行CYP1A2基因多态性检查,分析CYP1A2*1F与肺癌术后化疗效果及预后的相关性.[结果] ①100例患者,部分缓解 24例,稳定 44例,临床获益率为68.00%,患者CYP1A2*1F基因型以A/A型(49.00%)为主,其次为A/C型(38.00%);②临床获益患者中A/A基因型所占比例略高于未获益患者,但差异无显著性(P>0.05);③携带CYP1A2*1F A/A基因型患者总生存时间略高于A/C型、C/C型,但各组之间相比较差异无显著性(P>0.05).[结论] CYP1A2*1F突变基因型与肺癌术后化疗效果及预后无明显相关性.     

华南地区汉族人群心脑血管相关基因多态性分析

目的了解心脑血管相关基因细胞色素P450酶(CYP)2C19、CYP2C9、维生素K环氧化物还原酶复合体1(VKORC1)和乙醛脱氢酶2(ALDH2)基因的单核苷酸多态性频率在华南地区汉族人群分布的情况。方法采用芯片技术对252例心脑血管疾病患者的CYP2C19、ALDH2、CYP2C9以及VKORC1位点基因多态性进行检测,并统计男女间基因型频率的差异。结果 CYP2C19的野生型*1/*1占42.5%,突变型*1/*2占36.9%,*1/*3占7.9%,*2/*2占9.9%,*2/*3占1.6%,*3/*3占1.2%,在男女人群间各类基因型的发生率差异无统计学意义(P0.05);CYP2C9只检测到2种等位基因CYP2C9*1/*1和CYP2C9*1/*3,男性基因频率分别为98.6%和1.4%,女性基因频率分别为90.1%和9.9%,在男女人群间的分布差异有统计学意义(P0.05);VKORC1有3种基因型AA、AG和GG,频率分别为80.6%、18.7%和0.8%,在男女人群间的分布差异无统计学意义(P0.05);ALDH2有3种基因型GG、GL和LL型,频率分别为55.2%、37.3%和7.5%,在男女人群间的分布差异无统计学意义(P0.05)。结论 CYP2C9的多态性分布与性别有关,CYP2C19、VKORC1和ALDH2的多态性分布与性别无关。     

CYP3A4、CYP3A5和CYP2D6基因单核苷酸多态性对肾移植术后稳定期患者他克莫司代谢的影响

目的探讨肾移植患者细胞色素P450 CYP3A4、CYP3A5和CYP2D6基因单核苷酸多态性与他克莫司(FK506)代谢的相关性以及根据基因多态性制定FK506个体化治疗方案的可行性。方法收集随访的138例肾移植稳定期患者,均采用含FK506、吗替麦考酚酯、糖皮质激素的三联治疗方案。记录单位体重用药剂量数据、FK506谷浓度和CYP3A4、CYP3A5、CYP2D6基因单核苷酸多态性测序法检测结果。分析单核苷酸多态性与浓度调整的单位体重用药剂量的相关性。结果在138例患者中,CYP3A4野生型TT等位基因频率为0.993、杂合子TC等位基因频率为0.007;CYP3A5野生型AA等位基因频率为0.529、杂合子AG等位基因频率为0.399、纯合子GG等位基因频率为0.072;CYP2D6野生型(76例)CC等位基因频率为0.550、杂合子CT等位基因频率为0.449。为了达到相应的稳态浓度,CYP3A5野生型(AA)患者与突变型(AG、GG)相比需要更高剂量的FK506(P0.001);而CYP2D6野生型(CC)和突变型(CT)之间FK506剂量差异无统计学意义(P0.05)。结论CYP3A4的基因多态性以野生型常见,对FK506代谢的影响较少。CYP3A5的基因多态性与FK506的代谢密切相关,野生型患者需要较高剂量的FK506才能达到相应的稳态浓度。CYP2D6的基因多态性与FK506代谢无明显相关性。     

沈阳地区高血压患者CYP3A5基因多态性与钙离子通道阻滞剂氨氯地平的相关性研究

目的探讨CYP3A5基因多态性检测与钙离子通道阻滞剂氨氯地平用药指导的相关性研究。方法收集该院2016年1月至2018年12月1 182例高血压患者CYP3A5基因多态性检测结果,根据其基因表型分成CYP3A5*1/*1(AA型,野生型杂合子)型组/CYP3A5*1/*3(AG型,突变型杂合子)型组/CYP3A5*3/*3(GG型,突变型纯合子)型组3个组别;对所有高血压患者给予氨氯地平口服4周,监测治疗前后及治疗中血压,监测数据应用SPSS19.0分析探讨其相关性。结果 (1)1 182例高血压患者中AA型组频率为7.53%;GA型组频率为35.11%;GG型组频率为57.36%;(2)AA型组显著有效11例,有效37例,总有效率54%;AG型组显著有效50例,有效240例,总有效率70%;GG型组显著有效130例,有效487例,总有效率91%。氨氯地平对GG组疗效与其他两组比较差异有统计学意义(P0.05),3组疗效中GG组最好,AG组次之,AA组较差。结论 CYP3A5基因多态性可作为高血压患者选用氨氯地平药物的参考指标。     

东莞地区汉族冠心病患者CYP2C19基因多态性分布特征分析

目的探讨东莞地区汉族冠心病患者CYP2C19基因多态性分布特征。方法选取该院2016年9月至2019年1月收治的800例汉族冠心病患者作为研究对象,采用等位基因特异PCR技术对患者CYP2C19基因多态性进行检测,了解CYP2C19基因多态性分布情况,并根据患者的年龄、性别进行分组分析。结果 CYP2C19基因型中*1/*1出现频率为38.50%,*1/*2频率为40.00%,*1/*3频率为6.38%,*2/*2频率为11.75%,*2/*3频率为3.00%,*3/*3频率为0.37%;其中快代谢型为38.50%、中代谢型为46.38%、慢代谢型为15.12%;等位基因分布中CYP2C19*1占61.69%,CYP2C19*2占33.25%,CYP2C19*3占5.06%。不同年龄、性别、患者CYP2C19各基因多态性分布虽存在一定的差异,但差异无统计学意义(P>0.05)。结论东莞地区汉族人群冠心病患者CYP2C19基因型中以快代谢型与中代谢型为主,基因分布以CYP2C19*1占比较高,不同性别、年龄患者CYP2C19基因型间差异不明显。     

中国人群CYP1A1基因Exon7多态性及吸烟与肺癌易感性的关系

目的探讨中国人群CYP1A1基因Exon7位点多态性及吸烟与肺癌易感性的关系。方法制订纳入标准和排除标准,计算机检索中国期刊网全文数据库(CKNI)、万方数据库、维普数据库、Pubmed数据库建库至2014年1月的相关文献,并结合文献追溯等方法,收集关于中国人群CYP1A1基因Exon7位点多态性与肺癌的关系且有吸烟分型的病例-对照研究。统计对应的吸烟组及非吸烟组的研究数据,采用Stata10.0软件对各研究原始结果进行统计处理,计算合并OR值及95%置信区间(95%CI)。结果共纳入7篇中文、1篇英文文献,均为病例-对照研究。吸烟组中,突变型基因(Val/Val+Ile/Val)与野生型基因(Ile/Ile)比较,其合并OR值为1.759,95%CI(1.389,2.226);而该位点在非吸烟组中的合并OR值为1.256,95%CI(0.946,1.668)。结论 CYP1A1基因Exon7位点多态性可能与肺癌易感性有关,且CYP1A1基因Exon7位点多态性与吸烟在肺癌的发生中有协同作用。     

中国沈阳地区汉族冠心病患者CYP2C19基因多态性分布特征

目的探讨沈阳地区汉族冠心病(coronary heart disease,CHD)患者细胞色素P450 2C19(CYP2C19)基因多态性分布特征。方法选取2016年1月～2018年1月于北部战区总医院(原沈阳军区总医院)入院接受治疗的冠心病患者2 748例,应用聚合酶链反应微阵列芯片杂交方法检测患者氯吡格雷代谢相关的CYP2C19基因型。根据性别、年龄因素对患者进行分组。采用四格表资料的χ~2检验,R×C表资料的χ~2检验比较各组间冠心病患者氯吡格雷代谢相关的CYP2C19*1,*2,*3基因型,*2,*3等位基因频率,及氯吡格雷代谢型的分布差异。结果沈阳地区汉族冠心病患者CYP2C19*1/*1,CYP2C19*1/*2,CYP2C19*1/*3,CYP2C19*2/*2,CYP2C19*3/*3和CYP2C19*2/*3发生率分别为41.7%,39.3%,5.8%,9.8%,0.4%和3.0%;CYP2C19*2,CYP2C19*3等位基因频率分别为31.0%和4.8%;氯吡格雷快代谢型(EM),氯吡格雷中间代谢型(IM),氯吡格雷慢代谢型(PM)发生率分别为41.7%,45.1%和13.2%。根据性别分组,患者CYP2C19*2,*3等位基因,氯吡格雷代谢型,CYP2C19的6种基因型在不同性别冠心病患者中的分布差异均无统计学意义(χ~2=0.032～9.205,均P0.05)。根据年龄分组45岁,45～59岁,60～75岁,75岁,患者CYP2C19*2,*3等位基因,CYP2C19的6种基因型在不同年龄冠心病患者中的分布差异均有统计学意义(χ~2=17.718～48.772,均P≤0.001),氯吡格雷代谢型在不同年龄冠心病患者中的分布差异无统计学意义(χ~2=4.442,P=0.617)。结论沈阳地区汉族冠心病患者CYP2C19的6种基因型,CYP2C19*2,*3等位基因分布与沈阳地区汉族冠心病患者性别差异无关,与年龄分层密切相关。     

药物代谢酶基因多态性与初治急性髓系白血病初次诱导治疗结果的相关性研究

本研究目的是研究药物代谢酶基因多态性与初治急性髓系白血病(AML)初次诱导治疗结果的相关性,以113名初治急性髓系白血病患者为研究对象,采用SNP分型系统对药物代谢酶的11个单核苷酸多态性位点进行基因分型。应用逻辑回归比较各基因型分布情况与患者初次诱导治疗缓解率的关系。结果表明,多因素分析结果显示CYP2D6(rs16947)多态性位点的非野生型患者缓解率明显低于野生型患者,差异具有统计学意义(p=0.033,OR=0.32,95%CI 0.112-0.915);GSTO2(rs156697)多态性位点非野生型缓解率明显高于野生型患者,差异具有统计学意义(p=0.011,OR=3.023,95%CI 1.289-7.089);将两基因多态性位点进行联合分析,结果显示CYP2D6为非野生型基因且GSTO2野生型基因型(V+W)患者的缓解率明显低于两基因均为野生型(W+W)患者,差异具有统计学意义(p=0.017,OR=0.183,95%CI 0.045-0.735)。结论:CYP2D6(rs16947)和GSTO2(rs156697)基因多态性是影响初治急性髓系白血病初次诱导化疗缓解的独立因素。     

CYP2C19*17多态性对氯吡格雷临床疗效影响的系统评价

目的系统评价CYP2C19*17多态性对服用氯吡格雷治疗的心血管疾病患者临床疗效的影响。方法计算机检索EMbase、PubMed、h e Cochrane Library、ClinicalTrials.gov、CBM、CNKI、WanFang Data和VIP数据库,查找有关CYP2C19*17多态性对氯吡格雷疗效影响的研究,检索时限均为建库至2012年10月。由2位研究者按照纳入与排除标准独立筛选文献、提取资料和评价质量后,采用RevMan 5.2软件进行Meta分析。结果最终纳入6篇文献共7个研究,包含12116例患者,其中CYP2C19*17携带者5578例,CYP2C19*17非携带者6538例。Meta分析结果显示:与CYP2C19*17非携带者相比,CYP2C19*17突变携带者服用氯吡格雷心血管事件发生风险降低[OR=0.85,95%CI(0.73,0.99),P=0.03],但出血性事件发生风险增加[OR=1.25,95%CI(1.05,1.50),P=0.01]。结论服用氯吡格雷治疗的CYP2C19*17基因突变心血管疾病患者,其心血管事件发生风险相对较低,但出血性事件发生风险相对较高。     

A Km mutant of arylsulfatase A

Semi-micro techniques are presented for the genotyping of galactokinase and galactose-1-phosphate uridyltransferase. Radioactive assays are used to quantitate the levels of enzyme activity, while agarose gel electrophoresis is used to type the variants of galactose-1-phosphate uridyltransferase. All three methods can be performed on 1 ml whole blood, making the procedures ideal for use in confirmation of galactosemia or galactokinase deficiency in newborn screening programs.     

Hepatitis A: A preventable threat

Hepatitis A is a major public health problem, particularly in the pediatric population. Although hepatitis A infection does not cause chronic liver disease, it is associated with significant morbidity. The virus is transmitted primarily by person-to-person contact via the fecal-oral route. The infection can be inapparent, subclinical, anicteric, or icteric. In general, the severity of the disease is inversely correlated with the age of the child. Occasionally, fulminant hepatitis, which is associated with a high mortality rate, may result. The diagnosis of acute hepatitis A is most commonly made through the detection of immunoglobulin M (IgM) anti-hepatitis A antibody. Treatment is generally supportive. General preventive measures include improved standards of hygiene and sanitation. Universal childhood vaccination is the most effective method for eradicating hepatitis A and preventing its transmission.     

RHD845A/1227A基因型个体家系调查分析

本研究对1例RHD845A/1227A基因型个体进行家系调查分析,并分析他们的遗传特性。通过盐水法和间接抗人球蛋白试验（IAT）检测RH（D）抗原,PCR—SSP法检测RHD1227A和RHD845A等位基因以及RHD合子型,基因测序方式分析RIHD基因编码区序列。研究结果表明：血清学检测发现1例RH（D）抗原盐水法检测阴性、IAT法检测阳性样本,经RHD基因编码序列分析发现,RHD第845位与第1227位均出现G／A碱基杂合现象,推测该个体基因型可能为RHD845A／1227A。家系调查显示,先证者父亲为RHD阴性,母亲为RHD阳性。PCR-SSP检测结果显示,父亲携带RHDl227A等位基因,基因型为RHD845A／RHD-;母亲携带RHD845A等位基因,基因型为RHD845A／RHD＋,证明先证者分别从父亲和母亲遗传RHD1227A和RHD845A等位基因,基因型为RHD845A／1227A。结论：经过家系调查分析发现了1例罕见的RHD845A／1227A基因型个体。根据家系调查证明,RHD845A和RHD1227A等位基因分别由遗传获得,而非由个体基因变异形成。     

Potential Therapeutic Applications of Adenosine A2A Receptor Ligands and Opportunities for A2A Receptor Imaging

Adenosine A_2A receptors (A_2ARs) are highly expressed in the human striatum, and at lower densities in the cerebral cortex, the hippocampus, and cells of the immune system. Antagonists of these receptors are potentially useful for the treatment of motor fluctuations, epilepsy, postischemic brain damage, or cognitive impairment, and for the control of an immune checkpoint during immunotherapy of cancer. A_2AR agonists may suppress transplant rejection and graft‐versus‐host disease; be used to treat inflammatory disorders such as asthma, inflammatory bowel disease, and rheumatoid arthritis; be locally applied to promote wound healing and be employed in a strategy for transient opening of the blood–brain barrier (BBB) so that therapeutic drugs and monoclonal antibodies can enter the brain. Increasing A_2AR signaling in adipose tissue is also a potential strategy to combat obesity. Several radioligands for positron emission tomography (PET) imaging of A_2ARs have been developed in recent years. This review article presents a critical overview of the potential therapeutic applications of A_2AR ligands, the use of A_2AR imaging in drug development, and opportunities and limitations of PET imaging in future research.     

A PHYSIOLOGICO-PATHOLOGICAL STUDY OF A CASE OF HEART-BLOCK OCCURRING IN A DOG AS A RESULT OF NATURAL CAUSES

What is believed to be the first known case of heart-block arising in a dog as a result of an ingenerate pathological lesion is here reported. The auriculo-ventricular dissociation was of that degree known as relatively complete block and became apparent on section of the right vagus nerve. Stimulation of the peripheral end of the cut vagus failed to inhibit the ventricles, although complete inhibition of the auricles occurred. The same results were obtained during the ventricular acceleration produced by strophanthin, so that the failure of the vagus to inhibit the ventricles is not due to the latter''s infrequent action, but more probably to a normal lack of direct chronotropic influence upon the ventricular muscle. These findings are similar to those obtained by Erlanger in experimental heart-block. To small repeated doses of strophanthin injected intravenously the heart reacted as follows: (a) irregular slowing of the auricles and conversion of the relatively complete into an absolutely complete a-v block; (b) a rise in the irritability of the cardiac muscle manifested by a rapidly progressing auricular and ventricular frequency, the ventricular frequency surpassing ultimately the auricular frequency; (c) complete arrest of the auricles, the ventricles continuing at their high rate; (d) sudden fibrillation of the ventricles and shortly afterwards arrest in diastole. There were found post mortem myxomatous-like thickenings at the free edge of the septal tricuspid leaflet and at the attached margin of the posterior aortic leaflet and along part of the right anterior aortic leaflet. There was also a grayish patch on the right side of the auricular septum above the auriculo-ventricular junction. The thickenings at the edge of the valves consisted of dense, circumscribed masses of what appeared to be new connective tissue. The same tissue was found pressing against the bundle along the greater part of the latter''s course. There was considerable fatty infiltration of the auricular musculature immediately above the bundle and, to a slight extent, of the bundle itself. The fibers of communication between the auricular muscle and the node of Tawara were relatively few as compared with those of the normal heart. A review of the pathology of heart-block is appended, showing the present status of the question, concerning the relationship existing between disease of the a-v conducting system and the various grades of heart-block.